Cancer is a complex disease with extensive genetic and epigenetic defects, the archive of both of which are rapidly updated by the 2nd generation sequencing based genome-wide analyses at the DNA sequence, DNA methylation state, and protein and RNA expression levels. At the epigenetic level, a DNA sequence-independent mechanism that underlies the cross-cell generational transmission of gene expression memory, DNA methylation (addition of a methyl group at the cytosine ring of the 5′-CpG-3′ dinucleotides) is the best characterized and regarded as a promising molecular indicator for both diagnosis and/or prognostic of cancer. micro-RNAs (miRs) are small noncoding RNAs that regulate at both stability and translation levels in a sequence-specific manner the expression of protein-coding genes, including those controlling the DNA methylation. DNA methylation at the promoter region of a subset of miR genes negatively correlates with their transcription.
Hepatocellular carcinoma (HCC) is one of the most aggressive and common malignancies, having the second highest cancer mortality rate worldwide. Surgical removal of tumors followed by systemic chemotherapy is a preferred treatment for patients with localized disease. Patients with advanced disease are routinely treated by transarterial chemoembolization and systemic chemotherapy using doxorubicin, cisplatin, interferon, or 5-fluorouracil (5-FU), despite their uncertain clinical benefits. New molecular agents and antibodies targeting the defective signaling pathways have also been attempted for treating HCC, so far with limited success. Therefore, there is a compelling need for a robust diagnostics for early detection and (stratification) staging of the disease to maximize clinical benefits and minimize toxicity and cost of nonsurgical treatments.